Japan has been plunging into such an aging society as has never existed to date and has come to encounter the spread of such osteolytic diseases as osteoporosity as a serious social issue. The term "osteolytic disease" means diseases of bones induced by abnormal aggravation of osteolysis such as, for example, malignant hypercalcemia causes by myeloma and lymphoma, Paget's disease caused by local osteolysis, and osteoporosis caused by various factors like aging and menopause. The growth in the number of aged persons laid up in bed on account of bone fractures which originate in such osteolytic diseases ultimately results in a huge addition to the national medical expenses. At present, vitamin D preparation, calcitonin preparation, and ipriflavone preparation are being used for the therapy of these diseases. The treatment with these medicines allows no radical cure but barely serves as a symptomatic measure. The osteoarthritis, femoral head necrosis, and rheumatoid arthritis form a group of diseases which occur when the articular cartilage and cartilaginified bone are aggravated until degeneration and necrosis by various factors such as, for example, mechanical stress, aging, and inflammation and ultimately suffered to induce defects of bones and cartilages. These chondral defects, by deforming joints and causing pains therein, have a conspicuous effect in the degradation of the quality of daily life of the affected persons. Though the diseases of this category are being treated with hyaluronic acid, anti-inflammatory agent, and analgesic agent, a medicine which is capable of effectively inhibiting or curing chondral defects has not yet been developed.
The object of this invention, therefore, is to improve the existing method of therapy and to provide a novel and more effective preventive and therapeutic medicine.
The present inventors formerly discovered that a substance exhibiting a powerful activity to repress osteolysis is contained in the hops and that the active principle of this substance is an .alpha. acid and an iso .alpha. acid represented by the following general formula (XIII) (JP-A-07-330594). ##STR2##
(wherein R.sub.1 represents 2-methylpropyl group, 2-propyl group, or 2-butyl group).
It has been pointed out, however, that since the substance (XIII) effective in actively repressing the osteolysis mentioned above is a natural product, it tends to entail such problems as the dependency of the harvest of hops on weather conditions and the difficulty incurred in the procurement thereof. The inventors, with the expectation that the compounds approximating closely to this substance have the possibility of affording active substances as powerful as the aforementioned substance (XIII) capable of repressing osteolysis, have tried structural alterations of the active substance (XIII) mentioned above, synthesized many compounds, and tested them for activity. As a result, they have discovered powerful activity in the polyhydroxyphenol derivatives represented by the general formulas (I)-(XII) to be described herein below. The present invention has been perfected based 0n this discovery.